Incidence of and risk factors for paediatric perioperative anaphylaxis in the USA.

BACKGROUND: Perioperative anaphylaxis is a serious and often life-threatening immediate hypersensitivity reaction. There are few published data on paediatric perioperative anaphylaxis (pPOA). We evaluated the incidence of and risk factors involved in the occurrence of pPOA within a large US national database. METHODS: Deidentified data from the US Nationwide Inpatient Sample from 2005 to 2014 were used to identify pPOA cases and to conduct a retrospective multivariate analysis of preselected independent variables. RESULTS: Among 3,601,180 surgeries and procedures in children aged 0-18 yr, 297 pPOA cases were identified for an incidence of one in 12,125 surgeries and procedures. Compared with controls, pPOA cases had an increased median length of stay (6 vs 2 days; P<0.001) and median hospital cost ($54 719 vs $5109; P<0.0001). The age groups between 6 and 12 yr (odds ratio [OR] 7.1; 95% confidence interval [CI] 3.9-12.9; P<0.001) and 13 and 17 yr (OR 8.5; 95% CI 4.7-15.2; P<0.001) were associated with increased odds of pPOA. Transplant (OR 46.3; 95% CI 20.8-102.9; P<0.001), cardiac (OR 16.4; 95% CI 7.5-35.9; P<0.001), and vascular (OR 15.2; 95% CI 7.5-30.7; P<0.001) procedures posed the highest risk for pPOA. Chronic pulmonary disease, coagulopathy, and fluid and electrolyte disorders were also associated with pPOA (OR 2.2; 95% CI 1.5-3.3; P<0.001). CONCLUSIONS: The incidence of pPOA was one in 12,125 cases. Risk factors included age, procedure type, and comorbidities.

Treatment of perioperative anaphylaxis: room for improvement?

Perioperative anaphylaxis is associated with significant morbidity and mortality. Prompt and appropriate treatment is required for optimal outcome. Despite general knowledge of this condition, delays occur in the administration of epinephrine and in particular the use of i.v. route of administration in the perioperative setting. Barriers should be addressed to allow prompt utilisation of i.v. epinephrine in perioperative anaphylaxis.

Let go of the myth: safety of indocyanine green for sentinel lymph node mapping in endometrial cancer.

OBJECTIVE: Sentinel lymph node mapping by intracervical indocyanine green injection is the preferred method for surgical staging in endometrial cancer. Adverse reactions to indocyanine green are extremely rare, and information about the safety of this tracer in patients with a history of other allergies, asthma, or comorbidities is limited. We aim to evaluate the rate of adverse reactions to indocyanine green injected during sentinel lymph node mapping in patients with endometrial cancer and review the etiology of such reactions. METHODS: All patients with endometrial cancer undergoing sentinel lymph node mapping with indocyanine green cervical stroma injection at the Mayo Clinic in Rochester, Minnesota between June 2014 and December 2018 were retrospectively evaluated. Any adverse reaction occurring intra-operatively or within 7 days after surgery was identified. A thorough chart review was performed by an allergy specialist physician for any patient with an allergic-type reaction. RESULTS: We included 923 patients of which 565 (61.2%) had a history of allergy to antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), other medications, and/or environmental exposures. Of 490 patients who had previously received contrast media, 25 (5.1%) had a history of an adverse reaction. No immediate anaphylaxis or other allergic reactions were observed after indocyanine green injection. 10 (1.1%) patients developed a transient skin reaction within 7 days after surgery. None of these patients had a history of contrast media reaction. Based on timing and clinical/peri-operative history of affected patients, it was determined that skin reactions were likely induced by other newly prescribed medications or contact sensitivity, not administration of indocyanine green. CONCLUSION: Indocyanine green injection for sentinel lymph node mapping in patients with endometrial cancer caused no immediate/delayed anaphylactic or other severe allergic reactions. This included patients with a history of other allergies, asthma, and comorbidities. The myth of iodine's relationship to allergic reactions must be refuted to allow indocyanine green use in patients with a history of contrast media or shellfish allergy.

Perioperative anaphylactic reactions to central venous and pulmonary artery catheters containing chlorhexidine, sulfadiazine, or latex: a historical cohort study.

PURPOSE: Central venous catheters (CVCs) and pulmonary artery catheters (PACs) containing chlorhexidine, silver sulfadiazine, or latex can cause perioperative anaphylaxis. We examined the incidence of and outcomes associated with anaphylaxis caused by CVCs/PACs. METHODS: In a historical cohort study, we retrospectively identified adult patients fitted with CVCs/PACs at the Mayo Clinics in Minnesota, Arizona, and Florida from 1 January 2008 to 1 March 2018. Potential and confirmed cases of perioperative anaphylactic reactions were individually reviewed and classified. RESULTS: During the study period, 39,505 procedures were performed during which CVCs/PACs were inserted. Of these, 2,937 patients with pre-existing chlorhexidine, sulfonamide (sulfa), and/or latex allergies had CVCs/PACs inserted that contained these substances. Perioperative anaphylaxis, in which CVCs/PACs were the confirmed or potential causative agent, occurred during 53 procedures. Seven patients had a preoperatively reported sulfa or latex allergy; no patients had a preoperative chlorhexidine allergy. Six of the seven patients with reported allergies to sulfa or latex had a CVC/PAC inserted that contained these substances. Twenty-four patients with anaphylaxis had postoperative allergic disease consultation; ten of these (42%) underwent skin testing. CONCLUSION: Perioperative anaphylactic reactions related to CVCs/PACs containing chlorhexidine, silver sulfadiazine, or latex were rare in this large historical cohort study. We identified 2,937 patients with pre-existing chlorhexidine, sulfa, and/or latex allergies and had CVCs/PACs inserted that contained these substances. Although few cases of perioperative anaphylaxis attributable to these substances were observed in patients with corresponding allergies, the potential for substantial complication exists. Providers should be aware of the potential for these hidden exposures.

RéSUMé: OBJECTIF: Les cathéters veineux centraux (CVC) et les cathéters artériels pulmonaires (CAP) contenant de la chlorhexidine, de la sulfadiazine argentique ou du latex peuvent provoquer une anaphylaxie périopératoire. Nous avons examiné l'incidence et les devenirs associés à l'anaphylaxie causée par les CVC/CAP. MéTHODE: Dans une étude de cohorte historique, nous avons identifié rétrospectivement des patients adultes chez lesquels un CVC/CAP avait été installé aux cliniques Mayo du Minnesota, de l'Arizona et de la Floride du 1er janvier 2008 au 1er mars 2018. Les cas potentiels et confirmés de réactions anaphylactiques périopératoires ont été examinés et classés individuellement. RéSULTATS: Au cours de la période à l'étude, 39 505 interventions ont été réalisées au cours desquelles des CVC/CAP ont été insérés. Parmi celles-ci, des CVC/CAP contenant de la chlorhexidine, des sulfamides et/ou du latex ont été insérés chez 2937 patients présentant des allergies préexistantes à ces substances. Une anaphylaxie périopératoire, dont l'agent causal confirmé ou potentiel était le CVC/CAP, s'est produite dans 53 interventions. Sept patients présentaient une allergie aux sulfamides ou au latex signalée avant l'opération; aucun patient n'a eu d'allergie préopératoire à la chlorhexidine. Un CVC/CAP contenant des sulfamides ou du latex a été inséré chez six des sept patients ayant signalé des allergies à ces substances. Vingt-quatre patients atteints d'anaphylaxie ont eu une consultation postopératoire pour une maladie allergique; dix d'entre eux (42 %) ont subi des tests cutanés. CONCLUSION: Les réactions anaphylactiques périopératoires liées aux CVC/CAP contenant de la chlorhexidine, de la sulfadiazine argentique ou du latex étaient rares dans cette vaste étude de cohorte historique. Nous avons identifié 2937 patients présentant des allergies préexistantes à la chlorhexidine, aux sulfamides et/ou au latex chez lesquels des CVC/CAP contenant ces substances ont été insérés. Bien que peu de cas d'anaphylaxie périopératoire attribuable à ces substances aient été observés chez des patients présentant des allergies correspondantes, il existe un risque de complication importante. Les fournisseurs doivent être conscients du potentiel de ces expositions cachées.

Perioperative management of mastocytosis.

PURPOSE: Patients with mastocytosis have an increased risk of anaphylaxis during surgical procedures with general anesthesia. Therefore, we reviewed the anesthesia course of a large cohort of patients with mastocytosis. METHODS: We retrospectively reviewed adult and pediatric patients with mastocytosis who underwent surgical procedures with general anesthesia at Mayo Clinic from January 1, 2000, through June 30, 2021. We also included any procedures with general anesthesia that occurred during the 3-year period preceding mastocytosis diagnosis and designated the patients who underwent these procedures as having an unknown diagnosis at the time of their surgical procedure. We analyzed whether patients received chronic antimediator treatment for mastocytosis and/or prophylactic medications before the procedures. We also determined whether medications indicative of mastocytosis-related adverse events were intraoperatively administered. RESULTS: We identified 113 patients who underwent 219 procedures during the study period; 25 procedures were performed before mastocytosis diagnosis. Of 194 procedures in patients with known mastocytosis, patients received chronic antimediator therapy and/or perioperative prophylactic medications for 178 (91.8%) procedures. Among these procedures, 10 were potentially complicated by mast cell activation, which was inferred from administration of inhaled albuterol (n = 3) or intravenous diphenhydramine (n = 8). In addition, there was only one case of intraoperative anaphylaxis which occurred in a patient who underwent anesthesia before mastocytosis diagnosis and therefore did not receive prophylaxis. CONCLUSION: Intraoperative anaphylaxis can be the first presenting sign of mastocytosis. Patients with mastocytosis who received chronic antimediator therapy and/or preoperative prophylactic medications had an uneventful surgical course.

Incidence of and risk factors for perioperative or periprocedural anaphylaxis in the United States from 2005 to 2014.

BACKGROUND: The estimated worldwide incidence of perioperative or periprocedural anaphylaxis (PA) is between 1 in 1250 and 1 in 20,000 procedures. OBJECTIVE: To evaluate the incidence of PA in the United States and compare patient characteristics and underlying risk factors using a large national database. METHODS: Using deidentified data from the nationwide inpatient sample from 2005 to 2014, we identified cases of PA through the International Classification of Diseases, Ninth Revision, Clinical Modification codes and conducted a retrospective analysis. RESULTS: Among 35,647,347 surgeries and procedures, there were 5458 (0.015%) PA cases identified. The incidence of PA was 15.3 cases per 100,000 procedures. When compared with controls, PA cases had an increased mortality (3.4% vs 1.4%; P < .001), median length of stay (5 vs 3 days; P < .001), and median hospital cost ($45,155 vs $24,734; P < .001). The age group between 18 and 34 years (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.13-1.58; P < .001) and female sex (OR, 1.40; 95% CI, 1.31-1.49; P < .001) were associated with increased odds of PA. Transplant (OR, 3.35; 95% CI, 2.59-4.34; P < .001), hematologic (OR, 1.63; 95% CI, 1.30-2.05; P < .001), vascular (OR, 1.49; 95% CI, 1.30-1.67; P < .001), and cardiac (OR, 1.47; 95% CI, 1.30-1.67; P < .001) procedures were at increased risk for PA. Several comorbidities were associated with PA including chronic pulmonary disease (OR, 1.41; 95% CI, 1.31-1.51; P < .001). CONCLUSION: The incidence of PA is 1 in 6531 procedures, with a mortality of 1 in 191,652 procedures. PA has worsening outcomes compared with controls. The risk factors of PA include age, sex, procedure type, and comorbidities.

Incidence and risk factors for near-fatal and fatal outcomes after perioperative and periprocedural anaphylaxis in the USA, 2005-2014.

BACKGROUND: The incidence of fatal and near-fatal outcomes after perioperative anaphylaxis is unknown in the USA. Previously identified risk factors of neuromuscular-blocker-induced fatal perioperative anaphylaxis include male sex, obesity, and use of beta blockers. We examined the incidence of fatal and near-fatal outcomes after perioperative anaphylaxis in the USA and the underlying risk factors using a large national database. METHODS: Using the Nationwide Inpatient Sample from 2005 to 2014, we identified cases of fatal and near-fatal perioperative anaphylaxis, defined as perioperative anaphylaxis cases complicated by respiratory or cardiac arrest, using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. RESULTS: Amongst 5223 perioperative anaphylaxis cases, the proportion of near-fatal or fatal cases attributable to perioperative anaphylaxis was 7.0% (95% confidence interval [CI]: 6.2-7.7), with near-fatal perioperative anaphylaxis cases accounting for 5.0% (95% CI: 4.4-5.6%) and fatal cases accounting for 2.0% (95% CI: 1.5-2.5%) of cases overall. Thus, the incidence of fatal or near-fatal perioperative anaphylaxis is 1.26 in 100 000 procedures. Risk factors for fatal or near-fatal perioperative anaphylaxis include age (≥65 yr); undergoing a cardiac procedure; and comorbid conditions of weight loss, non-metastatic solid tumours, metastatic cancer, paralysis, coagulopathy, renal failure, congestive heart failure, fluid and electrolyte disorder, and neurological disorders. Individuals with near-fatal or fatal perioperative anaphylaxis reactions had increased lengths of stay and hospital costs compared with controls. CONCLUSIONS: The incidence of fatal or near-fatal perioperative anaphylaxis in the USA was 1.26 in 100 000 procedures. Risk factors for fatal or near-fatal outcomes include older age, cardiac procedures, and specific comorbidities.

Obstetric Anesthetic Management for Parturients with Hereditary Angioedema: A Case Report and Suggested Protocol.

Hereditary angioedema (HAE) is a disease manifested by repeated episodes of localized submucosal or subcutaneous edematous episodes, potentially triggered by emotional stress, mechanical trauma, or intake of estrogens. We present our experience managing two parturients with HAE. Multidisciplinary care is essential for planning and executing the specialized care of these patients, and management included extensive planning among obstetric, anesthesiology, and allergy and immunology teams. Pregnancy has been shown to have a variable effect on triggering HAE episodes. First-line treatment includes C1 esterase inhibitor concentrate, which can also be used for prophylaxis in high-risk patients. Neuraxial analgesia is recommended to avoid general anesthesia and was established early in both individuals. Vaginal delivery was well tolerated without need for emergent treatment for angioedema symptoms.

Anaesthetic management of patients with pre-existing allergic conditions: a narrative review.

This narrative review seeks to distinguish the clinical patterns of pre-existing allergic conditions from other confounding non-allergic clinical entities, and to identify the potential related risks and facilitate their perioperative management. Follow-up investigation should be performed after a perioperative immediate hypersensitivity to establish a diagnosis and provide advice for subsequent anaesthetics, the main risk factor for perioperative immunoglobulin E (IgE)-mediated anaphylaxis being a previous uninvestigated perioperative immediate hypersensitivity reaction. The concept of cross-reactivity between drugs used in the perioperative setting and food is often quoted, but usually not supported by evidence. There is no reason to avoid propofol in egg, soy, or peanut allergy. The allergenic determinants have been characterised for fish, shellfish, and povidone iodine, but remain unknown for iodinated contrast agents. Iodinated drugs may be used in seafood allergy. Evidence supporting the risk for protamine allergy in fish allergy and in neutral protamine Hagedorn insulin use is lacking. Conversely, cross-reactivity to gelatin-based colloid may occur in α-gal syndrome. Atopy and allergic asthma along with other non-allergic conditions, such as NSAID-exacerbated respiratory disease, chronic urticaria, mastocytosis, and hereditary or acquired angioedema, are not risk factors for IgE-mediated drug allergy, but there is a perioperative risk associated with the potential for exacerbation of the various conditions.

The use of drug provocation testing in the investigation of suspected immediate perioperative allergic reactions: current status.

Suspected perioperative allergic reactions are often severe. To avoid potentially life-threatening re-exposure to the culprit drug, establishing a firm diagnosis and identifying the culprit is crucial. Drug provocation tests are considered the gold standard in drug allergy investigation but have not been recommended in the investigation of perioperative allergy, mainly because of the pharmacological effects of drugs such as induction agents and neuromuscular blocking agents. Some specialised centres have reported benefits of provocation testing in perioperative allergy investigation, but the literature on the subject is limited. Here we provide a status update on the use of drug provocation testing in perioperative allergy, including its use in specific drug groups. This review is based on a literature search and experiences of the authors comprising anaesthesiologists and allergists with experience in perioperative allergy investigation. In addition, 19 participating centres in the International Suspected Perioperative Allergic Reaction Group were surveyed on the use of provocation testing in perioperative allergy investigation. A response was received from 13 centres in eight European countries, New Zealand, and the USA. Also, 21 centres from the Australian and New Zealand Anaesthetic Allergy Group were surveyed. Two centres performed provocation routinely and seven centres performed no provocations at all. Nearly half of the centres reported performing provocations with induction agents and neuromuscular blocking agents. Drug provocation testing is being used in perioperative allergy investigation in specialised centres, but collaborations between relevant specialties and multicentre studies are necessary to determine indications and establish common testing protocols.

Management of suspected immediate perioperative allergic reactions: an international overview and consensus recommendations.

Suspected perioperative allergic reactions are rare but can be life-threatening. The diagnosis is difficult to make in the perioperative setting, but prompt recognition and correct treatment is necessary to ensure a good outcome. A group of 26 international experts in perioperative allergy (anaesthesiologists, allergists, and immunologists) contributed to a modified Delphi consensus process, which covered areas such as differential diagnosis, management during and after anaphylaxis, allergy investigations, and plans for a subsequent anaesthetic. They were asked to rank the appropriateness of statements related to the immediate management of suspected perioperative allergic reactions. Statements were selected to represent areas where there is a lack of consensus in existing guidelines, such as dosing of epinephrine and fluids, the management of impending cardiac arrest, and reactions refractory to standard treatment. The results of the modified Delphi consensus process have been included in the recommendations on the management of suspected perioperative allergic reactions. This paper provides anaesthetists with an overview of relevant knowledge on the immediate and postoperative management of suspected perioperative allergic reactions based on current literature and expert opinion. In addition, it provides practical advice and recommendations in areas where consensus has been lacking in existing guidelines.

Comparative epidemiology of suspected perioperative hypersensitivity reactions.

Suspected perioperative hypersensitivity reactions are rare but contribute significantly to the morbidity and mortality of surgical procedures. Recent publications have highlighted the differences between countries concerning the respective risk of different drugs, and changes in patterns of causal agents and the emergence of new allergens. This review summarises recent information on the epidemiology of perioperative hypersensitivity reactions, with specific consideration of differences between geographic areas for the most frequently involved offending agents.

Sulfonamide Drug Allergy.

PURPOSE OF REVIEW: We sought to review past and current literature on sulfonamide drug allergy and distill it in a practical manner to assist the clinician, specifically focusing on cross-reactivity and desensitization. RECENT FINDINGS: There do not appear to be consistent genetic markers to reliably predict features of or the presence hypersensitivity reactions. Recent evidence continues to alleviate early concerns cross-reactivity between sulfonamide antibiotics and non-antibiotics. Sulfonamide drug allergy is frequently encountered by the practicing clinician. For sulfonamide antibiotics, delayed rash is the most common clinical manifestation. There is no current evidence to support avoidance of all non-antibiotic sulfonamides in those with a reported allergy to sulfonamide antibiotics, although certain scenarios require caution. Available evidence supports the cautious reintroduction of sulfonamide antibiotics via desensitization, which is usually well tolerated and should be considered in those with strong indications for trimethoprim-sulfamethoxazole and a reported sulfonamide allergy.

Stepping down inhaled corticosteroids from scheduled to as needed in stable asthma: Systematic review and meta-analysis.

BACKGROUND: Many patients with asthma are potentially overtreated, which results in unnecessary cost and unnecessary exposure to drugs that may result in adverse events. Step down helps reduce overtreatment, may mitigate these harms, and is advocated by major guidelines. Unfortunately, data that support step down are sparse. OBJECTIVES: This systematic review aimed to examine the effect of stepping down from scheduled inhaled corticosteroids (ICS) to as-needed ICS in patients with stable asthma. METHODS: Several electronic databases were systematically searched in April 2014. Articles were screened independently in duplicate. Studies were required to have at least a 12-week follow-up duration and to have compared stepping down from scheduled ICS to as-needed ICS and maintenance of scheduled ICS. Patients were required to have stable asthma as evidenced by at least 4 weeks without asthma exacerbation before intervention. RESULTS: A total of 3025 abstracts were retrieved initially, 77 of which were retrieved for full-text screening. Of these, only two articles were found to be eligible for inclusion, both were randomized controlled trials. By using random effects meta-analysis, it was determined that, after a follow-up of 6-10 months, the relative risk of exacerbation of stepping down from scheduled to as-needed ICS was 1.32 (95% confidence interval [CI], 0.81-2.16; p = 0.27, I(2) = 0%). Those who did not step down had more symptom-free days (standard mean difference 0.26 [95% CI, 0.02-0.49; p = 0.03; I(2) = 22%]). CONCLUSION: There is currently insufficient evidence to associate stepping down from scheduled to as-needed ICS with a change in exacerbations, although it may lead to fewer symptom-free days.

Stepping down from inhaled corticosteroids with leukotriene inhibitors in asthma: a systematic review and meta-analysis.

BACKGROUND: The risks of using leukotriene receptor antagonists (LTRA) as part of a strategy for stepping down inhaled corticosteroid (ICS) are not well known. OBJECTIVE: To estimate the risk of asthma exacerbation in individuals with stable asthma who start LTRA when stopping ICS or reducing ICS dose. METHODS: We identified articles from a systematic review of English and non-English articles by using a number of data bases. We included randomized controlled trials with a stable asthma run-in period of 4 weeks or more and a follow-up period of at least 3 months. We included studies of individuals with stable asthma who stopped ICS and substituted LTRA (versus continuing ICS) and who reduced ICS while starting LTRA (versus placebo). RESULTS: The search strategy identified 1132 potential articles, of which 52 were reviewed at the full-text level, and four met criteria for inclusion. The single article that met the inclusion criteria for substitution of LTRA for ICS as a step-down strategy found a statistically increased risk of treatment failure of 30.3% for substituting LTRA compared with 20.2% for continuing ICS. The three articles that met the inclusion criteria for comparing LTRA versus placebo in patients with stable asthma who reduce ICS found a modestly decreased risk ratio that favored LTRA of 0.57 (95% confidence interval, 0.36-0.90; I(2) = 0%) in studies that only included individuals >15 years old. CONCLUSION: Only one study addressed the risk of substitution of LTRA for ICS in stable asthma, which limited any strong conclusions about this step-down strategy.

The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Current asthma guidelines suggest that patients and their providers consider decreasing or stopping controller medications when asthma is stable. OBJECTIVE: We sought to estimate the risk of asthma exacerbation in patients who stop low-dose inhaled corticosteroids (ICSs) compared with those who continue ICSs in randomized controlled trials. METHODS: We identified relevant trials from a systematic review of English-language and non-English-language articles using MEDLINE, EMBASE, and CENTRAL (inception to January 21, 2012). Articles were screened at the abstract and full-text level by 2 independent reviewers. We included randomized controlled trials with a stable asthma run-in period of 4 weeks or more, an intervention to stop or continue ICSs, and a follow-up period of at least 3 months. We pooled results using a random-effects meta-analysis. RESULTS: The search strategy identified 1798 potential articles, of which 172 were reviewed at the full-text level and 7 met the criteria for inclusion. The relative risk for an asthma exacerbation in patients who stopped ICSs compared with those who continued use was 2.35 (95% CI, 1.88-2.92; P < .001; I(2) = 0%), as determined by using data pooled from trials with a mean follow-up of 27 weeks. The pooled absolute risk difference for an asthma exacerbation was 0.23 (95% CI, 0.16-0.30; P < .001; I(2) = 44%). Patients who discontinued ICSs also had a decreased FEV1 of 130 mL (95% CI, 40-210 mL; P = .003; I(2) = 53%), a decreased mean morning peak expiratory flow of 18 L/min (95% CI, 6-29 L/min; P = .004; I(2) = 82%), and an increased mean standardized asthma symptom score of 0.43 SDs (95% CI, 0.28-0.58 SDs; P < .001; I(2) = 0%). CONCLUSION: Patients with well-controlled asthma who stop regular use of low-dose ICSs have an increased risk of an asthma exacerbation compared with those who continue ICSs.

A US-Based Multicenter Retrospective Report of Perioperative Anaphylaxis, 2010-2021.

BACKGROUND: US-based perioperative anaphylaxis (POA) studies are limited to single-center experiences. A recent report found that a serum acute tryptase (sAT) >9.8 ng/mL or mast cell activation (MCA) can predict POA causal agent identification. Urinary mast cell mediator metabolites (uMC) have not been studied in POA. OBJECTIVE: To analyze the epidemiologic data of POA, to determine if sAT or MCA can predict suspected causal agent identification, and to evaluate uMC utility in POA. METHODS: This study is a retrospective multicenter review of POA cases that were subcategorized by suspected causal agent identification status. sAT, MCA (defined as sAT >2 + 1.2 × serum baseline tryptase), and uMC (N-methylhistamine [N-MH], 11ß-prostaglandin-F2α [11ß-PGF2α], leukotriene E4 [LTE4]) were recorded. RESULTS: Of 100 patients (mean age 52 [standard deviation 17] years, 94% adult, 50% female, 90% White, and 2% Hispanic) with POA, 73% had an sAT available, 41% had MCA, 16% had uMC available, and 50% had an identifiable suspected cause. POA cases with an identifiable suspected cause had a positive MCA status (100% vs 78%; P = .01) compared with POA with an unidentifiable cause. An elevated median sAT did not predict causal agent identification. Positive uMC were not associated with suspected causal agent identification during POA. Patients with positive uMC had a higher median sAT (30 vs 6.45 ng/mL; P = .001) and MCA status (96% vs 12%; P = .001) compared with negative uMC patients. Patients with POA had an elevated acute/baseline uMC ratios: 11ß-PGF2α ratio > 1.6, N-MH ratio >1.7, and LTE4 ratio >1.8. CONCLUSIONS: The presence of MCA in POA is associated with suspected causal agent identification. Positive uMC possibly correlate with a higher sAT level and MCA status but require further study. The authors suggest applying an acute/baseline uMC ratio (11ß-PGF2α ratio >1.6, N-MH ratio >1.7, and LTE4 ratio >1.87) in patients with POA for MCA when a tryptase level is inconclusive during POA evaluations.

Predicting Penicillin Allergy: A United States Multicenter Retrospective Study.

BACKGROUND: Using the reaction history in logistic regression and machine learning (ML) models to predict penicillin allergy has been reported based on non-US data. OBJECTIVE: We developed ML positive penicillin allergy testing prediction models from multisite US data. METHODS: Retrospective data from 4 US-based hospitals were grouped into 4 datasets: enriched training (1:3 case-control matched cohort), enriched testing, nonenriched internal testing, and nonenriched external testing. ML algorithms were used for model development. We determined area under the curve (AUC) and applied the Shapley Additive exPlanations (SHAP) framework to interpret risk drivers. RESULTS: Of 4777 patients (mean age 60 [standard deviation: 17] years; 68% women, 91% White, and 86% non-Hispanic) evaluated for penicillin allergy labels, 513 (11%) had positive penicillin allergy testing. Model input variables were frequently missing: immediate or delayed onset (71%), signs or symptoms (13%), and treatment (31%). The gradient-boosted model was the strongest model with an AUC of 0.67 (95% confidence interval [CI]: 0.57-0.77), which improved to 0.87 (95% CI: 0.73-1) when only cases with complete data were used. Top SHAP drivers for positive testing were reactions within the last year and reactions requiring medical attention; female sex and reaction of hives/urticaria were also positive drivers. CONCLUSIONS: An ML prediction model for positive penicillin allergy skin testing using US-based retrospective data did not achieve performance strong enough for acceptance and adoption. The optimal ML prediction model for positive penicillin allergy testing was driven by time since reaction, seek medical attention, female sex, and hives/urticaria.

Outcomes of stepping down asthma medications in a guideline-based pediatric asthma management program.

BACKGROUND: Little is known about outcomes after stepping down asthma medications within an asthma management program. OBJECTIVE: To determine outcomes of stepping down asthma medications in a pediatric asthma management program. METHODS: We performed a retrospective study of 5- to 18-year-old children with asthma in an integrated primary care practice in the United States. Data were included on participants from March 1, 2009, until December 31, 2011. We first determined whether a child was eligible for step down and next recorded whether a step-down attempt was made and if the attempt was successful. In addition to descriptive statistics for the sample demographics and the outcomes of stepping down, univariate and multivariate analyses were performed to determine predictors of successful asthma medication step-down attempts. RESULTS: Of the 477 children sampled for this study, 264 (55.3%) had a guideline-eligible opportunity to step down asthma medications. An attempted step down occurred in only 89 (33.7%) of children who had guideline-eligible opportunities. A total of 166 children (34.8%) attempted a step down of asthma medication at least once (including those guideline ineligible to step down). Of children with follow-up, 96 (71.6%) of step-down attempts were successful. Time of year (any season except fall) when the step down was attempted predicted successful step down in univariate and multivariate analysis (odds ratio = 3.81; 95% confidence interval, 1.23-11.85; P = .02). Being guideline eligible for step down predicted successful step down in univariate analysis only (odds ratio = 2.51; 95% confidence interval, 1.16-5.43; P = .02). CONCLUSION: Our findings from this sample of children participating in an asthma management program suggest that stepping down asthma medication based on National Asthma Education and Prevention Program 3 guidelines is frequently successful.